Therapeutic Agents That Act by Altering Hormone Control Mechanisms Flashcards
Which are the Therapeutic Agents That Act by Altering Hormone Control Mechanisms?
● Danazol (Danocrine)
● Clophene citrate (Clomid)
● Tamoxifen (Nolvadex), Toremifene (Farestron), Fulvestrant (Faslodex)
● Anastrozole (Arimidex®), Letrozole, (Femara®), Examestane (Aromasin®)
● GnRH and Analogs: Leuprolide, Nafarelin, Gosrelin, Histrelin
● GnRH Antagonists: Cetrorelix (Cetrolix®), Ganirelix, Degarelix
● Bromocriptine mesylate (Parlodel®)
What are the main characteristics of Danazol (Danocrine)?
● Weak progestin & weak androgen (partial agonist) ● MOA = Acts directly on ovary to prevent synthesis of estrogen & progest. by inhibiting certain CYP450s ● Treatment of fibrocystic breast disease (prevent synthesis of estrogen) ● Treatment of endometriosis (although this indication has been widely replaced by the use of GnRH agonists (continuous mode of administration) ● S.E. = due to androgenic agonist effects: reduction in breast size, thickening of skin with increased oiliness, hair growth, deepening of voice
What are the main characteristics of Clomiphene citrate (Clomid®)?
● Adverse effects = hot flashes (due to hypothalamic block); breast tenderness & heavy menses (due to too much estrogen later in cycle) ● Caution: Visual symptoms : blurred or double vision, floaters, light sensitivity, scotoma
What are the main characteristics of: Tamoxifen (Nolvadex®) Toremifene(Fareston®) Fulvestrant (Faslodex®)?
● Tamoxifen - a drug of choice for tx of breast cancer ● Think of Tamoxifen as a SERM which is an antagonist at estrogen receptors in the breast, but a partial agonist at estrogen receptors in the endometrium and bone ● Prevents bone loss and does not produce adverse effects on serum lipids ● Used for treatment of breast cancers that are estrogen receptor-positive ● Fulvestrant = pure estrogen receptor antagonist; used in tamoxifen-resistant patients
What are the main characteristics of: Anastrozole (Arimidex®) Letrozole (Femara®) Examestane (Aromasin®)?
● Anastrozole & Letrozole = competitive, reversible inhibitors of aromatase (the enzyme that converts testosterone to estradiol) ● Examestane = irreversible aromatase inhibitor ● All 3 used in treating breast cancer in pts resistant to tamoxifen
What are the main characteristics of: GnRH and Analogs: Leuprolide Nafarelin Gosrelin Histrelin?
● Agonists!! at GnRH receptors
● Peptides
● Intermittent = stimulate FSH / LH release (IV or SC)
o Gonadorelin - used to treat infertility caused by hypothalamic hypogonadism) – program pump to admin.
● Continuous = inhibit FSH / LH release (use long-acting analogs or depot formulations)
o Leuprolide, Gosrelin: treat prostate cancer
▪ In men = increase in serum testosterone levels for about 1-2 weeks; can precipitate pain in men with bone metastases or prostate “flare-up”
▪ In women = get hot flashes/sweats o Suppress endogenous FSH/LH release and give exogenous FSH/LH to correct timing for fertilization
What are the main characteristics of
GnRH Antagonists:
Cetrorelix (Cetrolix®)
Ganirelix
Degarelix?
● Pure GnRH receptor antagonist
● MOA: bind to pituitary GnRH receptors to
competitively inhibit FSH / LH release
● Used for In vitro fertilization (prevents LH surge &
premature ovulation), Endometriosis, Uterine fibroids
What are the main characteristics of Bromocriptine mesylate (Parlodel®)?
● Selective D-2 agonist (mimic effects of dopamine) → inhibits prolactin release from anterior pituitary
● Used for treatment of hyperprolactemia, Parkinson’s disease
● Caution: increased risk of stroke in post-partum women who do not want to lactate
